Safety of Ibuprofen After Major Orthopaedic Surgeries

NCT05575700 | Completed Phase 4 DMC

• 1 other identifier: 001CCWL2022
• Study Type: interventional
• Target: 2,904
• Locations: 1 country
• Sites: 11

Brief Summary

Safety of an eight-day treatment with ibuprofen after primary hip and knee arthroplasties.

Conditions

Hip Arthropathy; Knee Arthropathy; Safety Issues; Analgesia; Analgesic Adverse Reaction; Postoperative Pain; Postoperative Complications; Pain, Acute

Keywords

PERISAFE; Hip Arthroplasty; Knee Arthroplasty; Postoperative pain; Analgesia; Safety; Non-steroidal Anti-inflammatory drugs

Outcome Measures

Primary Outcomes (1)

• A composite outcome of either death, acute myocardial infarction, stroke, pulmonary embolism, deep venous thrombosis, renal failure, major bleeding, re-operation, gastrointestinal ulcer, or readmission within 90 days postoperatively.

  Proportion of patients with one or more severe adverse events defined in the composite outcome of either death, acute myocardial infarction, stroke, pulmonary embolism, deep venous thrombosis, renal failure, major bleeding, re-operation, gastrointestinal ulcer, or readmission within 90 days postoperatively.

  Postoperative day 0 to 90.

Secondary Outcomes (4)

• Hospital free days within 90 days postoperatively.

  Postoperative day 0 to 90.

• A composite outcome of ibuprofen related adverse events based on an eight-day postoperative diary: dyspepsia, diarrhoea.

  Postoperative day 0 to 8.

• A composite outcome of opioid related adverse events based on an eight-day postoperative diary: nausea, vomiting, constipation, dizziness, confusion, sedation, headache.

  Postoperative day 0 to 8.

• Health related quality of life questionnaire (EQ-5D-5L) after 90 days

  Postoperative day 90.

Other Outcomes (1)

• Postoperative pain levels, analgesic treatment, and opioid consumption based on an eight-day postoperative diary.

  Postoperative day 0 to 8.

Study Arms (2)

Ibuprofen

EXPERIMENTAL

Participants received ibuprofen 400 mg tablet administered orally three times daily, with eight hour intervals, for eight days after surgery.

Drug: Ibuprofen

Placebo

PLACEBO COMPARATOR

Participants received identical placebo tablet administered orally three times daily, with eight hour intervals, for eight days after surgery.

Drug: Placebo

Interventions

Ibuprofen DRUG

400 mg tablet three times daily

Ibuprofen

Placebo DRUG

tablet three times daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients scheduled for elective primary hip and knee arthroplasty.
• Age ≥ 18 years.
• Planned postoperative treatment with NSAID.
• Negative pregnancy test for women in the fertile age.
• Informed consent.

You may not qualify if:

• Unable to understand or speak Danish.
• Allergy to or contraindications against ibuprofen.

Sponsors & Collaborators

• Naestved Hospital: lead

Study Sites (11)

Private Hospital Gildhøj

Brøndby, 2605, Denmark

Location

Bispebjerg Hospital

Copenhagen NV, 2400, Denmark

Location

Aalborg University Hospital

Farsø, 9640, Denmark

Location

Gentofte Hospital

Hellerup, 2900, Denmark

Location

Nordsjællands Hospital Hillerød

Hillerød, 3400, Denmark

Location

Zealand University Hospital

Køge, 4600, Denmark

Location

Næstved Hospital

Næstved, 4700, Denmark

Location

Odense University Hospital

Odense, 3900, Denmark

Location

Silkeborg Regional Hospital

Silkeborg, 8600, Denmark

Location

Svendborg Hospital

Svendborg, 5700, Denmark

Location

Vejle Sygehus

Vejle, 7100, Denmark

Location

MeSH Terms

Conditions

Acute Pain; Agnosia; Pain, Postoperative; Postoperative Complications

Interventions

Ibuprofen

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases; Pathologic Processes

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Ole Mathiesen, Professor

  Zealand University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study medication will be masked by the pharmacy. The experimental medicine will be packed and labelled by Region Hovedstadens Pharmacy in accordance with the Good Manufacturing Practice regulations. The sponsor has a set of sealed, opaque envelopes with the participants' allocation, and these will only be revealed for the investigators when the data has been analysed and abstracts and conclusions covering the different possibilities for interpreting the trial results, have been agreed upon by the steering committee
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2022
• First Posted: October 12, 2022
• Study Start: April 17, 2023
• Primary Completion: August 19, 2025
• Study Completion: August 19, 2025
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Nine month after the trial has ended, and the primary results article has been published The study protocol and statistical analysis plan will be available after they have been published. Study protocol will be available at PERISAFE website.
• Access Criteria: We will make anonymized data available to other researchers' trough public database such as Zenodo open data repository (CERN), or another equivalent database. Furthermore, researchers wishing to access data from the PERISAFE trial should contact omat@regionsjaelland.dk in the first instance.

Locations

DK (11)